Antimicrobial Thermoplastic Polyuethanes

ABSTRACT

The disclosed technology provides thermoplastic polyurethane compositions having non-leaching antimicrobial properties while still maintaining good physical properties, methods of making the same, and articles, including medical devices, made from such compositions. The disclosed technology includes a process of making an antimicrobial polymer composition, where the process includes mixing an antimicrobial additive into a polymeric material; wherein said polymeric material comprises a polymeric backbone made up of urethane linkages derived from a polyisocyanate and a polyol; and wherein said mixing occurs under conditions that result in the breaking of a minority of said urethane bonds resulting in reactive isocyanate groups; and wherein two or more of said reactive isocyanate groups react with said antimicrobial additive to covalently bond said antimicrobial additive into the polymeric backbone of said polymeric material; resulting in an antimicrobial polymer composition.

FIELD OF THE INVENTION

The disclosed technology provides thermoplastic polyurethane (TPU)compositions having non-leaching antimicrobial properties while stillmaintaining good physical properties, methods of making the same, andarticles made from such compositions.

BACKGROUND

Antimicrobials are chemical compounds that reduce and/or mitigate thegrowth or development of microbial organisms. Antimicrobial additiveswork by a variety of mechanisms dependent upon the mode of action,composition, degree of activity, and application. When used properly,antimicrobial compounds lead to the death or arrested growth of thetargeted microorganisms. Since their discovery in the early 1900s,antimicrobials have transformed the prevention and treatment ofinfectious diseases. Antimicrobial additives are currently used across avery wide array of applications, including the use of antimicrobials inthe polymeric materials used in various medical applications. Forexample, polymeric materials that include antimicrobial additives can beused to make articles and devices for medical applications that willthen eliminate, reduce and/or mitigate the growth or development ofmicrobial organisms and so assist in the prevention and treatment ofinfectious diseases, including detrimental infections on medicalimplants and devices.

However, antimicrobials may also be hazardous to human health.Therefore, there is a need for antimicrobial additives that do not leachout of the materials in which they are used. Further there is a need forantimicrobial additives which do not leach out of the materials in whichthey are used and which remain effective over the life of usage of thematerial, or the article or device made from the material in which theantimicrobial additive is used.

Ideally, the antimicrobial agents that provide these non-leachingantimicrobial properties would have a proven history of use andeffective activity against various microorganisms without any adverseeffect on patients' health. The antimicrobial material, or othermaterials containing the antimicrobial additive, should be applicable tomedical or other health care product and/or surface thereof bycommercially-viable manufacturing methods such as molding, extrusion,and all other thermoplastic methods of ‘conversion’ or solvent-basedprocessing, water-borne systems, and 100%-solids (crosslinkable) liquid.In addition, the antimicrobial additive should not interfere with thephysiochemical and/or mechanical properties of the treated material,medical or other health care product and/or surface there.

Bacterial infection is a common complication related to the use ofmedical devices. Advances in various medical devices, including but notlimited to catheters, vascular access devices, peripheral lines,intravenous (IV) sites, drains, gastric feeding tubes, trachea tubes,stents, guidewires, pacemakers, and other implantable devices, havebenefited diagnostic and therapeutic medical care. However, bacterialinfections are becoming a serious and common complication related to theuse of medical devices, especially those implanted and/or used insidethe patient with a compromised defense system.

One approach to reduce device-related infections is to develop surfaceswith bactericidal activity, for example by making or coating the surfacewith a material that will elute and/or release antimicrobial compounds.Almost all treatments fall into one of the following threecategories: 1) adsorption of the antimicrobial additive into the surfaceof materials passively or in combination with surfactants or by way ofsurface-bonded polymers; 2) incorporation of the antimicrobial additiveinto a polymer coating applied on the material surface; 3) compoundingthe antimicrobial additive into the bulk material comprising the device.

However, all of these approaches are based on a leaching mechanism wherethe antimicrobial additive leaches out of the material in which it hasbeen added. This means the antimicrobial performance of the material isgenerally dependent on the concentration of the antimicrobial additive(loading) and the rate of its release from the material to which it hasbeen added. It is often very difficult to control the release rate andmaintain a constant level of concentration at the surface as the releaserate depends on many factors such as actual concentration, solubility,and diffusivity of these active ingredients in the bulk polymer whichmay also change over the time of use. All of these issues meanapproaches based on this leaching mechanism are often ineffective.

Therefore, a simple and cost effective method to create an antimicrobialcomposition that is useful for medical applications, and which is notdependent on a leaching mechanism to provide its antimicrobialproperties is needed.

SUMMARY

The disclosed technology provides thermoplastic polyurethane (TPU)compositions having non-leaching antimicrobial properties while stillmaintaining good physical properties, methods of making the same, andarticles made from such compositions.

The disclosed technology provides a process of making an antimicrobialpolymer composition, where said process includes the step of: (a) mixingan antimicrobial additive into a polymeric material; wherein thepolymeric material includes a polymeric backbone made up of urethanelinkages derived from a polyisocyanate and a polyol; and where themixing occurs under conditions that result in the breaking of a minorityof said urethane bonds resulting in reactive isocyanate groups; andwherein two or more of said reactive isocyanate groups react with saidantimicrobial additive to covalently bond said antimicrobial additiveinto the polymeric backbone of said polymeric material; resulting in anantimicrobial polymer composition.

In some embodiments, given the means by which the antimicrobial additiveis reacted into the backbone of the polymeric backbone, theantimicrobial properties of the resulting antimicrobial polymercomposition are substantially or completely non-leaching and thephysical properties of the antimicrobial polymer composition can bepreserved.

The disclosed technology further discloses the described process wherethe antimicrobial additive includes a deprotonated guanidine compound, adeprotonated biguanidine compound, or a mixture thereof. Thesedeprotonated compounds may be partially deprotonated guanidine and/orbiguanidine compounds, fully deprotonated guanidine and/or biguanidinecompounds, or mixtures thereof. In some embodiments, the antimicrobialadditive is deprotonated polyhexamethylene biguanide (PHMB), alsoreferred to as free base PHMB, and in some embodiments the antimicrobialadditive is free of protonated PHMB.

The disclosed technology further discloses the described process wherethe antimicrobial additive includes deprotonated PHMB.

The disclosed technology further discloses the described process wherethe polymeric material includes a thermoplastic polyurethane derivedfrom (a) a polyisocyanate component, (b) a polyol component, and (c) anoptional chain extender component.

The disclosed technology further discloses the described process wherethe polymeric material includes a thermoplastic polyurethane derivedfrom (a) diphenylmethane diisocyanate or a hexamethylene diisocyanate,(b) a polyether polyol, and (c) a butane diol component. In someembodiments where the polyether polyol is an aromatic polyether polyol.

The disclosed technology further discloses the described process wherethe mixing occurs at a temperature from 160 to 225 degrees Celsius. Themixing may also occur from 180 to 225, or from 160 to 200 degreesCelsius. In some embodiments, the range of temperatures where the mixingoccurs is important in order to incorporate the antimicrobial additivesinto the polymeric material in such a way that the additive is reactedin to the backbone of the polymeric material but the urethane linkagesin the polymeric materials do not reverted to such a degree thatextensive crosslinking occur, impacting the physical properties of thepolymeric material.

The disclosed technology further discloses the described process wherethe mixing occurs in an extruder where the antimicrobial additive isadded to the polymeric material and wherein said mixing occurs at atemperature between 180 and 225 degrees Celsius, where the extrudercomprises a twin screw extruder with co-rotating, self-wiping screws,with a mixture of conveying and mixing elements, and a length todiameter ratio of 20:1 to 50:1.

The disclosed technology further discloses the described process wherethe antimicrobial additive comprises a deprotonated guanidine compound,a deprotonated biguanidine compound, or a mixture thereof; where thepolyisocyanate which is inevitably liberated from reversal of thepolyurethane bond as the polyurethane is extruded at the temperaturesindicated and where the polyisocyanate reacts with said antimicrobialadditive and said polymeric material to covalently bond saidantimicrobial additive to the polymeric backbone of said polymericmaterial; and where the mixing occurs at a temperature between 180 and225 degrees Celsius, or even from 190 to 210 degrees Celsius.

The disclosed technology further discloses the described process wherethe antimicrobial additive includes polyhexamethylene biguanide,deprotonated polyhexamethylene biguanide, partially deprotonatedpolyhexamethylene biguanide or a combination thereof; where thepolymeric material includes a thermoplastic polyurethane derived from(a) diphenylmethane diisocyanate, (b) a polyether polyol, and (c) abutane diol component; and where the mixing occurs in an extruder wherethe antimicrobial additive is added to the polymeric material andwherein said mixing occurs at a temperature between 180 and 225 degreesCelsius, where the extruder comprises a twin screw extruder withco-rotating, self-wiping screws, with a mixture of conveying and mixingelements, and a length to diameter ratio of 20:1 to 50:1.

The disclosed technology further discloses the described process wherethe resulting antimicrobial polymer composition is non-leaching asdetermined by exhibiting a zero zone of inhibition in the AATCC 147Assessment of Antimicrobial Finishes on Textile Materials: ParallelStreak Method.

The disclosed technology further discloses an antimicrobial polymercomposition made from a polymeric material and an antimicrobialadditive, where the polymeric material comprises a polymeric backbonecomprising urethane linkages derived from a polyisocyanate and a polyol;and where at least some of the antimicrobial additive is covalentlybonded into said polymeric backbone of the polymeric material by two ormore linkages between the nitrogen atoms of the guanide or biguanide andthe isocyanate.

The disclosed technology further discloses the described compositionwhere the antimicrobial additive includes a deprotonated guanidinecompound, a deprotonated or partially deprotonated biguanidine compound,or a mixture thereof. These deprotonated compounds may be partiallydeprotonated guanidine and/or biguanidine compounds, fully deprotonatedguanidine and/or biguanidine compounds, or mixtures thereof. In someembodiments, the antimicrobial additive is deprotonatedpolyhexamethylene biguanide (PHMB), also referred to as free base PHMB,and in some embodiments the antimicrobial additive is free of protonatedPHMB.

The disclosed technology further discloses the described compositionwhere the antimicrobial additive includes deprotonated PHMB.

The disclosed technology further discloses the described compositionwhere the polymeric material includes a thermoplastic polyurethanederived from (a) a polyisocyanate component, (b) a polyol component, and(c) an optional chain extender component.

The disclosed technology further discloses the described compositionwhere the polymeric material includes a thermoplastic polyurethanederived from (a) diphenylmethane diisocyanate, hydrogenated MDI or ahexamethylene diisocyanate, (b) a polyether polyol, and (c) a butanediol component.

The disclosed technology further discloses the described compositionwhere the antimicrobial additive comprises a deprotonated guanidinecompound, a deprotonated biguanidine compound, or a mixture thereof;where the polyisocyanate which is liberated during the extrusion processat the temperatures indicated reacts with said antimicrobial additiveand said polymeric material to covalently bond said antimicrobialadditive to the polymeric backbone of said polymeric material.

The disclosed technology further discloses the described compositionwhere the antimicrobial polymer composition is non-leaching asdetermined by the AATCC 147 Assessment of Antimicrobial Finishes onTextile Materials: Parallel Streak Method.

The disclosed technology further discloses the described compositionwhere the antimicrobial additive includes a deprotonated guanidinecompound, a deprotonated biguanidine compound, or a mixture thereof;where the polymeric material comprises a thermoplastic polyurethanederived from (a) diphenylmethane diisocyanate, (b) a polyether polyol,and (c) a butane diol component.

The disclosed technology further discloses the articles made with theantimicrobial polymer composition described herein. In some embodiments,the articles are made from antimicrobial polymer compositions made froma polymeric material and an antimicrobial additive, where the polymericmaterial includes a polymeric backbone comprising urethane linkagesderived from a polyisocyanate and a polyol; and where the antimicrobialadditive is covalently bonded into said polymeric backbone of thepolymeric material by two or more urethane (or carbamate) linkages.

The disclosed technology further discloses the described article wherethe antimicrobial additive includes a deprotonated guanidine compound, adeprotonated biguanidine compound, or a mixture thereof; where thepolymeric material comprises a thermoplastic polyurethane derived from(a) diphenylmethane diisocyanate, (b) a polyether polyol, and (c) abutane diol component.

The disclosed technology further discloses the described article wherethe antimicrobial polymer composition described herein is coated onto amaterial and/or surface forming the article.

DETAILED DESCRIPTION

Various preferred features and embodiments will be described below byway of non-limiting illustration.

The disclosed technology provides thermoplastic polyurethane (TPU)compositions having non-leaching antimicrobial properties while stillmaintaining good physical properties, methods of making the same, andarticles made from such compositions.

The disclosed technology provides a process of making an antimicrobialpolymer composition, where said process includes the step of: (a) mixingan antimicrobial additive into a polymeric material; wherein thepolymeric material includes a polymeric backbone made up of urethanelinkages derived from a polyisocyanate and a polyol; and where themixing occurs under conditions that result in the breaking of a minorityof said urethane bonds resulting in reactive isocyanate groups; andwherein two or more of said reactive isocyanate groups react with saidantimicrobial additive to covalently bond said antimicrobial additiveinto the polymeric backbone of said polymeric material; resulting in anantimicrobial polymer composition.

The Antimicrobial Additive

The antimicrobial additives for use in the disclosed technology provideantimicrobial properties to the polymeric materials into which they areincorporated, and they have at least two groups and/or reactive sitesthat can react with isocyanate groups to form covalent bonds. This iswhat allows them to react into the backbone of the polymeric materialsdescribed here and what results in the described antimicrobial polymercompositions.

Suitable antimicrobial additive includes deprotonated guanidinecompounds, deprotonated biguanidine compounds, or a mixture thereof.These deprotonated compounds may be partially deprotonated guanidineand/or biguanidine compounds, fully deprotonated guanidine and/orbiguanidine compounds, or mixtures thereof. In some embodiments, theantimicrobial additive is deprotonated polyhexamethylene biguanide(PHMB), also referred to as free base PHMB (one example of which iscommercially available from Matrix). In some embodiment, theantimicrobial additive may also include protonated guanidine and/orbiguanidine compounds. In other embodiments, the antimicrobial additiveis substantially free of or even completely free of protonated guanidineand/or biguanidine compounds.

In addition to the antimicrobial additive described above, one or moreadditional antimicrobial additives may be used in the compositionsdescribed herein. These additives would not react into the backbone inthe way that those additives described will, but the additionalantimicrobial additives could be added to the compositions in moreconvention ways, including (i) adsorption of the antimicrobial additiveto the surface of materials passively or in combination with surfactantsor by way of surface-bonded polymers; (ii) incorporation of theantimicrobial additive into a polymer coating applied on the materialsurface; (iii) compounding the antimicrobial additive into the bulkmaterial comprising the device.

Suitable antimicrobial additives that may be used as these additionalantimicrobial additives are not overly limited.

They can be organic or organometallic compounds such as quaternaryammonium salts, phenols, alcohols, aldehydes, iodophores, poly quats(such as oligermeric poly quats derivatized from an ethylenicallyunsaturated diamine and an ethylenically unsaturated dihalo compound),biguanides, benzoates, parabens, sorbates, propionates, imidazolidinylurea, 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride(Dowacil 200, Quaternium), isothiazolones, DMDM hydantoin(2,3-imidazolidinedione), phenoxyethanol, bronopol, fluoroquinolones(such as ciprofloxacin), “potent” beta-lactams (third and fourthgeneration cephalosporins, carbapenems), beta-lactam/beta-lactamaseinhibitors, glycopeptides, aminoglycosides, antibiotic drugs, heparin,phosphorylcholine compounds, sulfobetaine, carboxybetaine, andorganometallic salts selected from silver salts, zinc salts, and coppersalts and their derivatives. Examples of these antimicrobial agentsincludes pharmaceutical drugs such as penicillin, trichlosan, functionalbiguanides, mono-functional polyquaterniums, quaternized mono-functionalpolyvinylpyrrolidones (PVP), silane quaternary ammonium compounds, andother quaternized ammonium salts.

In one embodiment, the additional antimicrobial additive is a quaternaryammonium molecule disclosed in U.S. Pat. No. 6,492,445 B2 (incorporatedherein by reference).

Further examples of suitable mono-functional antimicrobial compoundsinclude 2-hydroxyethyldimethyldodecylammonium chloride,2-hydroxyethyldimethyl octadecylammonium chloride, esterquats such asBehenoyl PG-trimonium chloride from Mason Chemical Company, Fluoroquats.Other small molecular diol bearing antimicrobial active centers can beincorporated into polyurethane backbone as chain extender. Examples ofsuch antimicrobial chain extender includes: diester quats such as Methylbis[ethyl(tallowate)]-2-hydroxyethyl]ammonium methylsulfate (CAS No.91995-81-2), Ethoquads such asOctadecylmethylbis(2-hydroxyethyl)ammonium chloride (CAS No. 3010-24-0),Oleyl-bis-(2-hydroxyethyl)methylammonium chloride,Polyoxyethylene(15)cocoalkylmethylammonium chloride (CAS No. 61791-10-4)available from Lion Akzo Co. Ltd, and the like.

However, in some embodiments no additional antimicrobial additives arepresent. Rather only the antimicrobial additives described above, whichhave at least two groups and/or reactive sites that can react withisocyanate groups to form covalent bonds, are used in the processesdescribed herein and to make the compositions described herein. In otherwords, in some embodiments the antimicrobial additive is free ofadditives that do not have at least two groups and/or reactive sitesthat can react with isocyanate groups to form covalent bonds.

The antimicrobial additive may be present in the compositions describedherein in any effective amount, that is, an amount that provides goodantimicrobial performance. In some embodiments, good antimicrobialperformance means a passing result in one or more of the tests describedherein. In some embodiments, the antimicrobial additive is present inthe described compositions from 0.1 to 10 percent by weight of theoverall composition, or from 0.1 to 5, or from 0.1 to 4 percent byweight. In other embodiments, the antimicrobial additive is present inthe described compositions from a lower limit of 0.1, 0.5, or 1.0 to anupper limit of 2.0, 4.0, 5.0, or 10 percent by weight. In someembodiments, the antimicrobial additive is present in the describedcompositions from 2.0 to 6.0 percent by weight. In still otherembodiments, the antimicrobial additive is present in the describedcompositions from a lower limit of 1.5 or 2.0 to an upper limit of 3.0or 3.5 percent by weight, or even 2.5 percent by weight.

The Polymeric Material

The disclosed technology makes and makes use of a polymeric material.The polymeric material is made up of a polymeric backbone, which itselfis made up of urethane linkages derived from a polyisocyanate and apolyol.

These linkages in the polymeric backbone of the polymeric material areimportant to the disclosed technology, as it is the reversion of a smallnumber of these linkages that create the active reaction sites which canthen react with the antimicrobial additives described above. Thefollowing reactions results in new polymeric material where theantimicrobial additives are bond directly into the polymeric backbone ofthe polymeric material, thus providing the non-leaching antimicrobialproperties to the overall composition.

Suitable polymeric materials for use in the processes, compositions, andarticles described herein may include any polymeric materials thatinclude urethane linkages derived from a polyisocyanate and a polyol inits backbone or polymer blends which contain one of the polymers in theblend which contains urethane linkages.

In some embodiments, the polymeric material includes a thermoplasticpolyurethane derived from (a) a polyisocyanate component, (b) a polyolcomponent, and (c) an optional chain extender component.

In some embodiments, the polymeric material includes a thermoplasticpolyurethane derived from (a) a polyisocyanate component, (b) a polyolcomponent.

In some embodiments, the polymeric material includes a thermoplasticpolyurethane derived from (a) a polyisocyanate component, (b) a polyolcomponent, and (c) a chain extender component.

The polyisocyanate component may contain one or more polyisocyanates.Suitable polyisocyanates include aromatic diisocyanates, aliphaticdiisocyanates, or combinations thereof.

In some embodiments, the polyisocyanate component includes one or morealiphatic diisocyanates. In some embodiments, the polyisocyanatecomponent is essentially free of, or even completely free of, aromaticdiisocyanates. In other embodiments, the polyisocyanate componentincludes one or more aliphatic diisocyanates in combination with one ormore aromatic polyisocyanate.

In some embodiments, the polyisocyanate component includes one or morearomatic diisocyanates. In some embodiments, the polyisocyanatecomponent is essentially free of, or even completely free of, aliphaticdiisocyanates. In other embodiments, the polyisocyanate componentincludes one or more aromatic diisocyanates in combination with one ormore aliphatic polyisocyanate.

Examples of useful polyisocyanate may include aromatic diisocyanatessuch as 4,4′-methylenebis(phenyl isocyanate) (MDI), m-xylenediisocyanate (XDI), phenylene-1,4-diisocyanate,naphthalene-1,5-diisocyanate, and toluene diisocyanate (TDI);3,3′-dimethyl-4,4′-biphenylene diisocyanate (TODI), 1,5-naphthalenediisocyanate (NDI), as well as aliphatic diisocyanates such ashexamethylene diisocyanate (HDI) 4,4′-Diisocyanato dicyclohexylmethane(HMDI), isophorone diisocyanate (IPDI), 1,4-cyclohexyl diisocyanate(CHDI), decane-1,10-diisocyanate, lysine diisocyanate (LDI), 1,4-butanediisocyanate (BDI), isophorone diisocyanate (PDI), anddicyclohexylmethane-4,4′-diisocyanate (H12MDI). Mixtures of two or morepolyisocyanates may be used. In some embodiments, the polyisocyanate isMDI and/or H12MDI. In some embodiments, the polyisocyanate includes MDI.In some embodiments, the polyisocyanate includes H12MDI.

In some embodiments, the mixtures of two or more polyisocyanates may beused.

In some embodiments, the thermoplastic polyurethane is prepared with apolyisocyanate component that includes HDI. In some embodiments, thethermoplastic polyurethane HDI prepared with a polyisocyanate componentthat consists essentially of H12MDI. In some embodiments, thethermoplastic polyurethane is prepared with a polyisocyanate componentthat consists of HDI.

In some embodiments, the polyisocyanate used to prepare the TPU and/orTPU compositions described herein is at least 50%, on a weight basis, acycloaliphatic diisocyanate. In some embodiments, the polyisocyanateincludes an a, w-alkylene diisocyanate having from 5 to 20 carbon atoms.

In some embodiments, the polyisocyanate used to prepare the TPU and/orTPU compositions described herein includeshexamethylene-1,6-diisocyanate, 1,12-dodecane diisocyanate,2,2,4-trimethyl-hexamethylene diisocyanate,2,4,4-trimethyl-hexamethylene diisocyanate, 2-methyl-1,5-pentamethylenediisocyanate, or combinations thereof.

In some embodiments, the described TPU is prepared with a polyisocyanatecomponent that includes HDI, H12MDI, LDI, IPDI, or combinations thereof.In some embodiments, the TPU is prepared with a polyisocyanate componentconsists of, or even consists essentially of HDI.

In still other embodiments, the polyisocyanate component is essentiallyfree of (or even completely free of) any non-linear aliphaticdiisocyanates, any aromatic diisocyanates, or both. In still otherembodiments, the polyisocyanate component is essentially free of (oreven completely free of) any polyisocyanate other than the linearaliphatic diisocyanates described above.

In some embodiments, the polyisocyanate component is diphenylmethanediisocyanate, H12MDI, hexamethylene diisocyanate, or a combinationthereof. In some embodiments, the polyisocyanate component isdiphenylmethane diisocyanate. In some embodiments, the polyisocyanatecomponent is hexamethylene diisocyanate.

The polyol component may contain one or more polyols. Polyols suitablefor use in the invention may include polyether polyols, polyesterpolyols, polycarbonate polyols, polysiloxane polyols, and combinationsthereof. Suitable polyols, which may also be described as hydroxylterminated intermediates, when present, may include one or more hydroxylterminated polyesters, one or more hydroxyl terminated polyethers, oneor more hydroxyl terminated polycarbonates, one or more hydroxylterminated polysiloxanes, or mixtures thereof.

Suitable hydroxyl terminated polyester intermediates include linearpolyesters having a number average molecular weight (Mn) of from about500 to about 10,000, from about 700 to about 5,000, or from about 700 toabout 4,000, and generally have an acid number less than 1.3 or lessthan 0.5. The molecular weight is determined by assay of the terminalfunctional groups and is related to the number average molecular weight.The polyester intermediates may be produced by (1) an esterificationreaction of one or more glycols with one or more dicarboxylic acids oranhydrides or (2) by transesterification reaction, i.e., the reaction ofone or more glycols with esters of dicarboxylic acids. Mole ratiosgenerally in excess of more than one mole of glycol to acid arepreferred so as to obtain linear chains having a preponderance ofterminal hydroxyl groups. Suitable polyester intermediates also includevarious lactones such as polycaprolactone typically made fromε-caprolactone and a bifunctional initiator such as diethylene glycol.The dicarboxylic acids of the desired polyester can be aliphatic,cycloaliphatic, aromatic, or combinations thereof. Suitable dicarboxylicacids which may be used alone or in mixtures generally have a total offrom 4 to 15 carbon atoms and include: succinic, glutaric, adipic,pimelic, suberic, azelaic, sebacic, dodecanedioic, isophthalic,terephthalic, cyclohexane dicarboxylic, and the like. Anhydrides of theabove dicarboxylic acids such as phthalic anhydride, tetrahydrophthalicanhydride, or the like, can also be used. Adipic acid is a preferredacid. The glycols which are reacted to form a desirable polyesterintermediate can be aliphatic, aromatic, or combinations thereof,including any of the glycols described above in the chain extendersection, and have a total of from 2 to 20 or from 2 to 12 carbon atoms.Suitable examples include ethylene glycol, 1,2-propanediol,1,3-propanediol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol,1,6-hexanediol, 2,2-dimethyl-1,3-propanediol, 1,4-cyclohexanedimethanol,decamethylene glycol, dodecamethylene glycol, and mixtures thereof.

The polyol component may also include one or more polycaprolactonepolyester polyols. The polycaprolactone polyester polyols useful in thetechnology described herein include polyester diols derived fromcaprolactone monomers. The polycaprolactone polyester polyols areterminated by primary hydroxyl groups. Suitable polycaprolactonepolyester polyols may be made from ε-caprolactone and a bifunctionalinitiator such as diethylene glycol, 1,4-butanediol, or any of the otherglycols and/or diols listed herein. In some embodiments, thepolycaprolactone polyester polyols are linear polyester diols derivedfrom caprolactone monomers.

Useful examples include CAPA™ 2202A, a 2,000 number average molecularweight (Mn) linear polyester diol, and CAPA™ 2302A, a 3,000 Mn linearpolyester diol, both of which are commercially available from PerstorpPolyols Inc. These materials may also be described as polymers of2-oxepanone and 1,4-butanediol.

The polycaprolactone polyester polyols may be prepared from 2-oxepanoneand a diol, where the diol may be 1,4-butanediol, diethylene glycol,monoethylene glycol, 1,6-hexanediol, 2,2-dimethyl-1,3-propanediol, orany combination thereof. In some embodiments, the diol used to preparethe polycaprolactone polyester polyol is linear. In some embodiments,the polycaprolactone polyester polyol has a number average molecularweight from 500 to 10,000, or from 500 to 3,000, or 600 to 1,000, or1,000 to 3,000 or from 500, or 600, or from 1,000 or even 2,000 to 4,000or even 3,000, or even about 2,000.

Suitable hydroxyl terminated polyether intermediates include polyetherpolyols derived from a diol or polyol having a total of from 2 to 15carbon atoms, in some embodiments an alkyl diol or glycol which isreacted with an ether comprising an alkylene oxide having from 2 to 6carbon atoms, typically ethylene oxide or propylene oxide or mixturesthereof. For example, hydroxyl functional polyether can be produced byfirst reacting propylene glycol with propylene oxide followed bysubsequent reaction with ethylene oxide. Primary hydroxyl groupsresulting from ethylene oxide are more reactive than secondary hydroxylgroups and thus are preferred. Useful commercial polyether polyolsinclude poly(ethylene glycol) comprising ethylene oxide reacted withethylene glycol, poly(propylene glycol) comprising propylene oxidereacted with propylene glycol, poly(tetramethylene ether glycol)comprising water reacted with tetrahydrofuran which can also bedescribed as polymerized tetrahydrofuran, and which is commonly referredto as PTMEG. In some embodiments, the polyether intermediate includesPTMEG. Suitable polyether polyols also include polyamide adducts of analkylene oxide and can include, for example, ethylenediamine adductcomprising the reaction product of ethylenediamine and propylene oxide,diethylenetriamine adduct comprising the reaction product ofdiethylenetriamine with propylene oxide, and similar polyamide typepolyether polyols. Copolyethers can also be utilized in the describedcompositions. Typical copolyethers include the reaction product of THFand ethylene oxide or THF and propylene oxide. These are available fromBASF as PolyTHF® B, a block copolymer, and PolyTHF® R, a randomcopolymer. The various polyether intermediates generally have a numberaverage molecular weight (Mn) as determined by assay of the terminalfunctional groups which is an average molecular weight greater thanabout 700, such as from about 700 to about 10,000, from about 1,000 toabout 5,000, or from about 1,000 to about 2,500. In some embodiments,the polyether intermediate includes a blend of two or more differentmolecular weight polyethers, such as a blend of 2,000 Mn and 1,000 MnPTMEG.

Suitable hydroxyl terminated polycarbonates include those prepared byreacting a glycol with a carbonate. U.S. Pat. No. 4,131,731 is herebyincorporated by reference for its disclosure of hydroxyl terminatedpolycarbonates and their preparation. Such polycarbonates are linear andhave terminal hydroxyl groups with essential exclusion of other terminalgroups. The essential reactants are glycols and carbonates. Suitableglycols are selected from cycloaliphatic and aliphatic diols containing4 to 40, and or even 4 to 12 carbon atoms, and from polyoxyalkyleneglycols containing 2 to 20 alkoxy groups per molecule with each alkoxygroup containing 2 to 4 carbon atoms. Suitable diols include aliphaticdiols containing 4 to 12 carbon atoms such as 1,4-butanediol,1,5-pentanediol, neopentyl glycol, 1,6-hexanediol,2,2,4-trimethyl-1,6-hexanediol, 1,10-decanediol, hydrogenateddilinoleylglycol, hydrogenated dioleylglycol, 3-methyl-1,5-pentanediol;and cycloaliphatic diols such as 1,3-cyclohexanediol,1,4-dimethylolcyclohexane, 1,4-cyclohexanediol-,1,3-dimethylolcyclohexane-, 1,4-endomethylene-2-hydroxy-5-hydroxymethylcyclohexane, and polyalkylene glycols. The diols used in the reactionmay be a single diol or a mixture of diols depending on the propertiesdesired in the finished product. Polycarbonate intermediates which arehydroxyl terminated are generally those known to the art and in theliterature. Suitable carbonates are selected from alkylene carbonatescomposed of a 5 to 7 member ring. Suitable carbonates for use hereininclude ethylene carbonate, trimethylene carbonate, tetramethylenecarbonate, 1,2-propylene carbonate, 1,2-butylene carbonate, 2,3-butylenecarbonate, 1,2-ethylene carbonate, 1,3-pentylene carbonate,1,4-pentylene carbonate, 2,3-pentylene carbonate, and 2,4-pentylenecarbonate. Also, suitable herein are dialkylcarbonates, cycloaliphaticcarbonates, and diarylcarbonates. The dialkylcarbonates can contain 2 to5 carbon atoms in each alkyl group and specific examples thereof arediethylcarbonate and dipropylcarbonate. Cycloaliphatic carbonates,especially dicycloaliphatic carbonates, can contain 4 to 7 carbon atomsin each cyclic structure, and there can be one or two of suchstructures. When one group is cycloaliphatic, the other can be eitheralkyl or aryl. On the other hand, if one group is aryl, the other can bealkyl or cycloaliphatic. Examples of suitable diarylcarbonates, whichcan contain 6 to 20 carbon atoms in each aryl group, arediphenylcarbonate, ditolylcarbonate, and dinaphthylcarbonate.

Suitable polysiloxane polyols include α-ω-hydroxyl or amine orcarboxylic acid or thiol or epoxy terminated polysiloxanes. Examplesinclude poly(dimethysiloxane) terminated with a hydroxyl or amine orcarboxylic acid or thiol or epoxy group. In some embodiments, thepolysiloxane polyols are hydroxyl terminated polysiloxanes. In someembodiments, the polysiloxane polyols have a number-average molecularweight in the range from 300 to 5,000, or from 400 to 3,000.

Polysiloxane polyols may be obtained by the dehydrogenation reactionbetween a polysiloxane hydride and an aliphatic polyhydric alcohol orpolyoxyalkylene alcohol to introduce the alcoholic hydroxy groups ontothe polysiloxane backbone.

In some embodiments, the polysiloxanes may be represented by one or morecompounds having the following formula:

in which: each R1 and R2 are independently a 1 to 4 carbon atom alkylgroup, a benzyl, or a phenyl group; each E is OH or NHR³ where R³ ishydrogen, a 1 to 6 carbon atoms alkyl group, or a 5 to 8 carbon atomscyclo-alkyl group; a and b are each independently an integer from 2 to8; c is an integer from 3 to 50. In amino-containing polysiloxanes, atleast one of the E groups is NHR³. In the hydroxyl-containingpolysiloxanes, at least one of the E groups is OH. In some embodiments,both R¹ and R² are methyl groups.

Suitable examples include α,ω-hydroxypropyl terminatedpoly(dimethysiloxane) and α,ω-amino propyl terminatedpoly(dimethysiloxane), both of which are commercially availablematerials. Further examples include copolymers of thepoly(dimethysiloxane) materials with a poly(alkylene oxide).

The polyol component, when present, may include poly(ethylene glycol),poly(tetramethylene ether glycol), poly(trimethylene oxide), ethyleneoxide capped poly(propylene glycol), poly(butylene adipate),poly(ethylene adipate), poly(hexamethylene adipate),poly(tetramethylene-co-hexamethylene adipate),poly(3-methyl-1,5-pentamethyl ene adipate), polycaprolactone diol,poly(hexamethylene carbonate) glycol, poly(pentamethylene carbonate)glycol, poly(trimethylene carbonate) glycol, dimer fatty acid basedpolyester polyols, vegetable oil based polyols, or any combinationthereof.

Examples of dimer fatty acids that may be used to prepare suitablepolyester polyols include Priplast™ polyester glycols/polyolscommercially available from Croda and Radia® polyester glycolscommercially available from Oleon.

In some embodiments, the polyol component includes a polyether polyol, apolycarbonate polyol, a polycaprolactone polyol, or any combinationthereof.

In some embodiments, the polyol component includes a polyether polyol.In some embodiments, the polyol component is essentially free of or evencompletely free of polyester polyols. In some embodiments, the polyolcomponent used to prepare the TPU is substantially free of, or evencompletely free of polysiloxanes.

In some embodiments, the polyol component includes ethylene oxide,propylene oxide, butylene oxide, styrene oxide, poly(tetramethyleneether glycol), poly(propylene glycol), poly(ethylene glycol), copolymersof poly(ethylene glycol) and poly(propylene glycol), epichlorohydrin,and the like, or combinations thereof. In some embodiments the polyolcomponent includes poly(tetramethylene ether glycol).

In other embodiments, the polyol component is essentially free of (oreven completely free of) any polyether polyols, polycarbonate polyols,polysiloxane polyols, or all of the above.

Suitable polyamide oligomers, including telechelic polyamide polyols,are not overly limited and include low molecular weight polyamideoligomers and telechelic polyamides (including copolymers) that includeN-alkylated amide groups in the backbone structure. Telechelic polymersare macromolecules that contain two reactive end groups. Amineterminated polyamide oligomers can be useful as polyols in the disclosedtechnology. The term polyamide oligomer refers to an oligomer with twoor more amide linkages, or sometimes the amount of amide linkages willbe specified. A subset of polyamide oligomers are telechelic polyamides.Telechelic polyamides are polyamide oligomers with high percentages, orspecified percentages, of two functional groups of a single chemicaltype, e.g. two terminal amine groups (meaning either primary, secondary,or mixtures), two terminal carboxyl groups, two terminal hydroxyl groups(again meaning primary, secondary, or mixtures), or two terminalisocyanate groups (meaning aliphatic, aromatic, or mixtures). Ranges forthe percent difunctional that can meet the definition of telechelicinclude at least 70, 80, 90 or 95 mole % of the oligomers beingdifunctional as opposed to higher or lower functionality. Reactive amineterminated telechelic polyamides are telechelic polyamide oligomerswhere the terminal groups are both amine types, either primary orsecondary and mixtures thereof, i.e. excluding tertiary amine groups.

In some embodiments, the polyol component is a polyether polyol. In someembodiments, the polyether polyol is PTMEG.

In some embodiments, the chain extender component may contain one ormore chain extenders. Chain extenders suitable for use in the inventionmay include at least one diol chain extender of the general formulaHO—(CH₂)_(x)—OH wherein x is an integer from 2 to 12 or even from 4 to6. In other embodiments, x is the integer 4.

Useful extenders also include diol chain extenders such as relativelysmall polyhydroxy compounds, for example lower aliphatic or short chainglycols having from 2 to 20, or 2 to 12, or 2 to 10 carbon atoms.Suitable examples include ethylene glycol, diethylene glycol, propyleneglycol, dipropylene glycol, 1,4-butanediol (BDO), 1,6-hexanediol (HDO),1,3-butanediol, 1,5-pentanediol, neopentylglycol,1,4-cyclohexanedimethanol (CHDM),2,2-bis[4-(2-hydroxyethoxy)phenyl]propane (HEPP), heptanediol,nonanediol, dodecanediol, ethylenediamine, butanediamine,hexamethylenediamine, and hydroxyethyl resorcinol (HER), and the like,as well as mixtures thereof. In some embodiments, the chain extenderincludes BDO, HDO, or a combination thereof. In some embodiments, thechain extender includes BDO. Other glycols, such as aromatic glycolscould be used, but in some embodiments the TPUs described herein areessentially free of or even completely free of such materials, or acombination thereof.

In some embodiments, the chain extender includes a cyclic chainextender. Suitable examples include CHDM, HEPP, HER, and combinationsthereof. In some embodiments, the chain extender may include an aromaticcyclic chain extender, for example HEPP, HER, or a combination thereof.In some embodiments, the chain extender may include an aliphatic cyclicchain extender, for example CHDM. In some embodiments, the chainextender is substantially free of, or even completely free of aromaticchain extenders, for example aromatic cyclic chain extenders. In someembodiments, the chain extender is substantially free of, or evencompletely free of polysiloxanes.

In some embodiments, the chain extender component is butane diol.

The Antimicrobial Polymeric Material

The polymeric material described herein generally include one or more ofthe thermoplastic polyurethane (TPU) materials described above.

The polymeric material may also include one or more additionalcomponents. These additional components include other polymericmaterials that may be blended with the TPU described herein. Theseadditional components also include one or more additives that may beadded to the TPU, or blend containing the TPU, to impact the propertiesof the composition.

The TPU described herein may also be blended with one or more otherpolymers. The polymers with which the TPU described herein may beblended are not overly limited. In some embodiments, the describedcompositions include a two or more of the described TPU materials. Insome embodiments, the compositions include at least one of the describedTPU materials and at least one other polymer, which is not one of thedescribed TPU materials. In some embodiments, the described blends willhave the same combination of properties described above for the TPUcomposition. In other embodiments, the TPU composition will of coursehave the described combination of properties, while the blend of the TPUcomposition with one or more of the other polymeric materials describedabove may or may not.

Polymers that may be used in combination with the TPU materialsdescribed herein also include more conventional TPU materials such asnon-caprolactone polyester-based TPU, polyether-based TPU, or TPUcontaining both non-caprolactone polyester and polyether groups. Othersuitable materials that may be blended with the TPU materials describedherein include polycarbonates, polyolefins, styrenic polymers, acrylicpolymers, polyoxymethylene polymers, polyamides, polyphenylene oxides,polyphenylene sulfides, polyvinyl chlorides, chlorinatedpolyvinylchlorides, polylactic acids, or combinations thereof.

Polymers for use in the blends described herein include homopolymers andcopolymers. Suitable examples include: (i) a polyolefin (PO), such aspolyethylene (PE), polypropylene (PP), polybutene, ethylene propylenerubber (EPR), polyoxyethylene (POE), cyclic olefin copolymer (COC), orcombinations thereof; (ii) a styrenic, such as polystyrene (PS),acrylonitrile butadiene styrene (ABS), styrene acrylonitrile (SAN),styrene butadiene rubber (SBR or HIPS), polyalphamethylstyrene, styrenemaleic anhydride (SMA), styrene-butadiene copolymer (SBC) (such asstyrene-butadiene-styrene copolymer (SBS) andstyrene-ethylene/butadiene-styrene copolymer (SEBS)),styrene-ethylene/propylene-styrene copolymer (SEPS), styrene butadienelatex (SBL), SAN modified with ethylene propylene diene monomer (EPDM)and/or acrylic elastomers (for example, PS-SBR copolymers), orcombinations thereof; (iii) a thermoplastic polyurethane (TPU) otherthan those described above; (iv) a polyamide, such as Nylon™, includingpolyamide 6,6 (PA66), polyamide 1,1 (PA11), polyamide 1,2 (PA12), acopolyamide (COPA), or combinations thereof; (v) an acrylic polymer,such as polymethyl acrylate, polymethylmethacrylate, a methylmethacrylate styrene (MS) copolymer, or combinations thereof; (vi) apolyvinylchloride (PVC), a chlorinated polyvinylchloride (CPVC), orcombinations thereof; (vii) a polyoxyemethylene, such as polyacetal;(viii) a polyester, such as polyethylene terephthalate (PET),polybutylene terephthalate (PBT), copolyesters and/or polyesterelastomers (COPE) including polyether-ester block copolymers such asglycol modified polyethylene terephthalate (PETG), polylactic acid(PLA), polyglycolic acid (PGA), copolymers of PLA and PGA, orcombinations thereof; (ix) a polycarbonate (PC), a polyphenylene sulfide(PPS), a polyphenylene oxide (PPO), or combinations thereof; orcombinations thereof.

In some embodiments, these blends include one or more additionalpolymeric materials selected from groups (i), (iii), (vii), (viii), orsome combination thereof. In some embodiments, these blends include oneor more additional polymeric materials selected from group (i). In someembodiments, these blends include one or more additional polymericmaterials selected from group (iii). In some embodiments, these blendsinclude one or more additional polymeric materials selected from group(vii). In some embodiments, these blends include one or more additionalpolymeric materials selected from group (viii).

The additional additives suitable for use in the TPU compositionsdescribed herein are not overly limited. Suitable additives includepigments, UV stabilizers, UV absorbers, antioxidants, lubricity agents,heat stabilizers, hydrolysis stabilizers, cross-linking activators,flame retardants, layered silicates, radio opacifiers, such as bariumsulfate, tungsten metal, non-oxide bismuth salts, fillers, colorants,reinforcing agents, adhesion mediators, impact strength modifiers,antimicrobials, and any combination thereof.

The TPU compositions described herein may also include additionaladditives, which may be referred to as a stabilizer. The stabilizers mayinclude antioxidants such as phenolics, phosphites, thioesters, andamines, light stabilizers such as hindered amine light stabilizers andbenzothiazole UV absorbers, and other process stabilizers andcombinations thereof. In one embodiment, the preferred stabilizer isIrganox®-1010 from BASF and Naugard®-445 from Chemtura. The stabilizeris used in the amount from about 0.1 weight percent to about 5 weightpercent, in another embodiment from about 0.1 weight percent to about 3weight percent, and in another embodiment from about 0.5 weight percentto about 1.5 weight percent of the TPU composition.

Still further optional additives may be used in the TPU compositionsdescribed herein. The additives include colorants, antioxidants(including phenolics, phosphites, thioesters, and/or amines),antiozonants, stabilizers, inert fillers, lubricants, inhibitors,hydrolysis stabilizers, light stabilizers, hindered amines lightstabilizers, benzotriazole UV absorber, heat stabilizers, stabilizers toprevent discoloration, dyes, pigments, inorganic and organic fillers,radioopacifiers, reinforcing agents and combinations thereof.

All of the additives described above may be used in an effective amountcustomary for these substances. These additional additives can beincorporated into the components of, or into the reaction mixture for,the preparation of the TPU resin, or after making the TPU resin. Inanother process, all the materials can be mixed with the TPU resin andthen melted or they can be incorporated directly into the melt of theTPU resin.

The Process

The disclosed technology includes a process for making the describedantimicrobial polymer compositions. The described process includes thestep of mixing one or more antimicrobial additives, which are describedabove, into a one or more polymeric materials, which are also describedabove. The polymeric material includes a polymeric backbone made up ofurethane linkages derived from a polyisocyanate and a polyol. The mixingoccurs under conditions that result in the breaking of a minority ofsaid urethane bonds resulting in reactive isocyanate groups. Two or moreof said reactive isocyanate groups react with said antimicrobialadditive to covalently bond said antimicrobial additive into thepolymeric backbone of said polymeric material. The resulting materialsis an antimicrobial polymer composition.

The disclosed technology provides the desired result of a non-leachingantimicrobial polymer composition when the antimicrobial additive hastwo or more of the described reactive groups capable of reacting withisocyanate groups and the mixing of the polymeric material and theantimicrobial additive is done under control conditions that result in asmall number of the urethane linkages in the polymeric backbone of thepolymeric material to reverse, or dissociate, and the relatively smallnumber of broken polymer chains that now have reactive isocyanate groupsreact with the antimicrobial additive such that new polymers are formedwhere the broken polymer backbones reform with the antimicrobialadditive present in the new backbone. Thus, the antimicrobial additiveis not present as a pendant group connected to or bonded to thepolymeric backbone. Further the antimicrobial additive is not present asa terminal group connected to or bonded to end of the polymeric chain.Rather the antimicrobial additive of the disclosed technology israndomly bonded into the backbone of the polymeric material itself.Still further, the benefits of the disclosed technology cannot beachieved if the antimicrobial additive is added during the synthesis ofthe polymeric material, as the antimicrobial additive would not beproperly disbursed throughout the backbones of the resulting polymericmaterial and/or would create unwanted side reactions during thesynthesis of the TPU. Also, since most antimicrobial additives have morethan two reactive sites, they would act as cross linkers, forming anunusable high crosslinked polymeric material unsuitable for the uses andapplications described herein. Finally, simply adding the antimicrobialadditive to the polymeric material under conditions that do not createthe backbone breaking and reforming described here would not result inpolymeric materials with the antimicrobial additives bonded into thebackbone, but rather only simple mixtures where the antimicrobialadditives is not bond to the polymeric material and where leaching wouldoccur.

The non-leaching antimicrobial polymeric compositions of the disclosedtechnology, where the antimicrobial additives are bonded into thebackbone of the polymeric material, are achieved by careful control ofthe conditions under which the polymeric material and antimicrobialadditive are mixed. Particularly the temperature of the extrusion andthe configuration of the extruder screw are important to insuring thatsufficient thermal energy to adequately reverse the urethane bonds toyield reactive isocyanate groups. The exact temperature and screwconfiguration which yields antimicrobial and non-leaching polymericproducts will depend on what type of isocyanate is used to produce theTPU in the formulation since it is well known by those skilled in theart that aliphatic urethane bonds reverse to give isocyanate groups at alower temperature than aromatic urethane bonds and as a result, if analiphatic TPU is used in the formulation, a lower temperature for theextrusion to produce the antimicrobial TPU can be used when compared toan aromatic TPU.

First, the thermoplastic polyurethanes of the invention can be preparedby processes which are conventional in the art for the synthesis ofpolyurethane elastomers such as but not limited to a two-step, batchprocess or a one-shot technique. In a two-step process, a prepolymerintermediate is reacted with an excess amount of diisocyanate, followedby chain extending the same. In the batch process, the components, i.e.,the diisocyanate(s), the polyol(s), and the chain extenders (s), as wellas the catalyst(s) and any other additive(s), if desired, are introducedinto a container, mixed, dispensed into trays and allowed to cure. Thecured TPU can then be granulated and pelletized. The one-shot procedureis performed in an extruder, e.g. single screw, twin screw, wherein theformative components, introduced individually or as a mixture into theextruder.

One or more polymerization catalysts may be present during thepolymerization reaction. Generally, any conventional catalyst can beutilized to react the diisocyanate with the polyol intermediates or thechain extender. Examples of suitable catalysts which in particularaccelerate the reaction between the NCO groups of the diisocyanates andthe hydroxy groups of the polyols and chain extenders are theconventional tertiary amines known from the prior art, e.g.triethylamine, dimethylcyclohexylamine, N-methylmorpholine,N,N′-dimethylpiperazine, 2-(dimethylaminoethoxy)ethanol,diazabicyclo[2.2.2]octane and the like, and also in particularorganometallic compounds, such as titanic esters, iron compounds, e.g.ferric acetylacetonate, tin compounds, e.g. stannous diacetate, stannousdioctoate, stannous dilaurate, or the dialkyltin salts of aliphaticcarboxylic acids, e.g. dibutyltin diacetate, dibutyltin dilaurate, orthe like. The amounts usually used of the catalysts are from 0.0001 to0.1 part by weight per 100 parts by weight of polyhydroxy compound (b).

The TPU materials described above may be prepared by a process thatincludes the step of (I) reacting: a) the polyisocyanate componentdescribed above, that includes at least one aliphatic diisocyanate; b)the polyol component described above, that includes at least onepolyester polyol; and c) the chain extender component described abovethat includes a substituted 2,5-diketopiperazine, as described above.

The process may further include the step of: (II) mixing the TPUcomposition of step (I) with one or more blend components, including oneor more additional TPU materials and/or polymers, including any of thosedescribed above.

The process may further include the step of: (II) mixing the TPUcomposition of step (I) with one or more additional additives selectedfrom the group consisting of pigments, UV stabilizers, UV absorbers,antioxidants, lubricity agents, heat stabilizers, hydrolysisstabilizers, cross-linking activators, flame retardants, layeredsilicates, fillers, colorants, reinforcing agents, adhesion mediators,impact strength modifiers, and antimicrobials.

The process may further include the step of: (II) mixing the TPUcomposition of step (I) with one or more blend components, including oneor more additional TPU materials and/or polymers, including any of thosedescribed above, and/or the step of: (III) mixing the TPU composition ofstep (I) with one or more additional additives selected from the groupconsisting of pigments, UV stabilizers, UV absorbers, antioxidants,lubricity agents, heat stabilizers, hydrolysis stabilizers,cross-linking activators, flame retardants, layered silicates, fillers,colorants, reinforcing agents, adhesion mediators, impact strengthmodifiers, and antimicrobials.

The process may further include in step I of including a co-extendercomponent that includes at least one diol chain extender of the generalformula HO—(CH₂)_(x)—OH wherein x is an integer from 2 to 6.

Once the TPU is ready, it can be used as the polymeric material of thedisclosed process and it can be mixed with the antimicrobial additivedescribed above.

The carefully controlled mixing conditions must effectively melt thepolymeric material, effectively mix the antimicrobial additive into thepolymeric material, and also effectively reverse, or dissociate, a smallnumber of urethane bonds in the backbone of the polymeric material.

In some embodiments, while not wishing to be bound by theory, applicantsbelieve there is a dissociating a small number of urethane bonds in thebackbone of the polymeric material. By this we mean, in someembodiments, less than 20% of all the bonds in the backbone of thepolymeric material, or less than 10%, or less than 5% or less than 2%.In other embodiments, it means from 0.1 to 20% of the bonds, or from 0.1to 10, 0.1 to 5, 0.1 to 2% of the urethane bonds. In other embodiments,it means from 1 to 20% of the bonds, or from 1 to 10, 1 to 5, 1 to 2% ofthe urethane bonds. In still other embodiments it means from about 0.1,0.2, 0.5, or 1% to 2, 3, or 5% of the urethane bonds. In someembodiments, dissociating a small number of urethane bonds in thebackbone of the polymeric material means from 0.1% to 2% or form 0.1 to5% of all the urethane bonds in the backbone of the polymeric material.For additional information on urethane bond breaking, see ChemicalReview, 2013, 113 (1), pp 80-118 and Macromolecular Materials andEngineering, 2003, 288 (6), pp 525-530, which are both incorporated byreference.

The disclosed technology further discloses the described process wherethe mixing occurs in a mixing device at a temperature from 160 to 225degrees Celsius. The mixing may also occur from 180 to 225, or from 160to 200 degrees Celsius.

In some embodiments, where the polymeric materials includes an aliphaticTPU (a TPU made from an aliphatic diisocyanate), the mixing occurs in amixing device at a temperature from 160 to 200 degrees Celsius. Themixing may also occur from 155 to 175, or from 160 to 180, or even from165 to 185 degrees Celsius.

In some embodiments, where the polymeric materials includes an aromaticTPU (a TPU made from an aromatic diisocyanate), the mixing occurs in amixing device at a temperature from 180 to 220 degrees Celsius. Themixing may also occur from 175 to 215, or from 180 to 220, or even from185 to 225 degrees Celsius.

The disclosed technology further discloses the described process wherethe mixing occurs in an extruder where the antimicrobial additive isadded to the polymeric material and wherein said mixing occurs at atemperature between 180 and 225 degrees Celsius, where the extrudercomprises a twin screw extruder with co-rotating, self-wiping screws,with a mixture of conveying and mixing elements, and a length todiameter ratio of 30:1 to 50:1. In other embodiments the describedprocess in the described extruder occurs at 160 to 200, 155 to 175, 160to 180, or 165 to 185 degrees Celsius. In other embodiments, thedescribed process in the described extruder occurs at 180 to 220, 175 to215, 180 to 220, or 185 to 225 degrees Celsius.

The Articles

The compositions described herein may be used in the preparation of oneor more articles. The specific type of articles that may be made fromthe TPU materials and/or compositions described herein are not overlylimited.

The invention further provides an article made with the TPU materialsand/or compositions described herein. Examples include but are notlimited to medical applications, as well as used in, personal careapplications, pharmaceutical applications, health care productapplications, or any other number of applications. These articles may beprepared by extruding, injection molding, or any combination.

In some embodiments, the compositions described herein are used to maketubular medical devices. Tubular medical articles within the meaning ofthe present invention are those medical articles that can conductfluids. In particular, the medical articles are selected from the groupconsisting of catheters, central venous catheters, peripheral venouscatheters, breathing tubes, stents, couplings, ports, conduit systems,connectors, spikes, valves, three-way stopcocks, syringes, conduits,injection ports, wound drains, thoracic drains and probes.

Other suitable medical articles that can be made using the compositionsof described here include central venous catheters; peripheral venouscatheters; breathing tubes, stents; products for application in regionalanesthesia, especially catheters, couplings, filters; products forinfusion therapy, especially containers, ports, conduit systems,filters; accessories, such as connectors, spikes, valves, three-waystopcocks, syringes, conduits, injection ports; products of formulation,especially transfer sets, mixing sets; urological products, especiallycatheters, urine measuring and collecting devices; wound drains; wounddressing; surgical suture materials; implantation auxiliaries as well asimplants, especially plastic implants, for example, hernia meshes,non-wovens, knitwear/knitted fabrics, ports, port catheters, vascularprostheses; disinfectants; disposable surgical instruments; thoracicdrains; probes; catheters; housings of medical devices, especiallyinfusion pumps, dialysis devices and screens; artificial dentures;containers for liquids, especially contact lens containers. Othersuitable applications for the compositions disclosed here include foodprocessing equipment and cosmetic materials.

In some embodiments, the compositions described herein are used to makePICC catheters and CVC catheters.

Antimicrobial Properties

Persons skilled in the art are well aware of what is meant by the term“antimicrobial.” Moreover, persons skilled in the art are familiar witha wide variety of chemical substances that have antimicrobialproperties. Nevertheless, Applicants provide a quantitative definitionof the term “antimicrobial” in the context of the present invention. Anantimicrobial additive of the present invention is an additive whichimparts to the polymer containing it the ability to reduce theconcentration of E. coli at the surface of the polymer by a factor of50%.

The disclosed technology further discloses the described process wherethe resulting antimicrobial polymer composition is non-leaching asdetermined by exhibiting a zero zone of inhibition in the AATCC 147Assessment of Antimicrobial Finishes on Textile Materials: ParallelStreak Method.

In other embodiments, the TPU materials and/or compositions describedherein may be used to produce medical devices, such as implants orcoatings on implants, where the TPU delivers one or more therapeuticagents at the site of implantation. The terms “therapeutic agents” and“drugs” are used herein interchangeably to mean any material that has atherapeutic effect at an implantation site. Also as used herein, thedevice of the present invention is said to “deliver” or “elute”therapeutic agent—these terms are used synonymously and generally torefer to any mechanism by which the therapeutic agent comes into contactwith tissue.

The therapeutic agent(s) may be delivered in a number of ways. In oneexample, the therapeutic agent(s) are embedded within a coating that ismade using the TPU materials and/or compositions described herein thatadheres to one or more surfaces of an implant or other medical articleor medical device. In some embodiments, the coating is made from one ormore of the TPU materials and/or compositions described herein admixedwith the therapeutic agent(s) such that the agent is eluted from thepolymer over time, or is released from the coating as it degradesin-vivo. In some embodiments one or more therapeutic agents are appliedin discrete areas on one or more individual section or surfaces of theimplant or other medical article or medical device.

The amount of each chemical component described is presented exclusiveof any solvent which may be customarily present in the commercialmaterial, that is, on an active chemical basis, unless otherwiseindicated. However, unless otherwise indicated, each chemical orcomposition referred to herein should be interpreted as being acommercial grade material which may contain the isomers, by-products,derivatives, and other such materials which are normally understood tobe present in the commercial grade.

According to the present invention, “substantially free” means that thedescribed material may be present in an amount below 1% by weight,preferably below 0.5% by weight, more preferably below 0.01% by weight,the weight percentages being based on the total weight of thecomposition for the preparation of the tubular medical article.

It is known that some of the materials described above may interact inthe final formulation, so that the components of the final formulationmay be different from those that are initially added. For instance,metal ions (of, e.g., a flame retardant) can migrate to other acidic oranionic sites of other molecules. The products formed thereby, includingthe products formed upon employing the composition of the technologydescribed herein in its intended use, may not be susceptible of easydescription. Nevertheless, all such modifications and reaction productsare included within the scope of the technology described herein; thetechnology described herein encompasses the composition prepared byadmixing the components described above.

Examples

The technology described herein may be better understood with referenceto the following non-limiting examples.

The examples provided below are evaluated to determine if they arenon-eluting by the zone of inhibition (ZOI) test and also tested todetermine their antimicrobial performance by various tests including JISZ2801, the QualityLab Certika™ Assay and/or the Innovotech BEST™ Assay.

Materials:

The following materials were used in the preparation of Examples 1 to 3:

(1) free base PHMB, (deprotonated) PHMB obtained from Matrix.(2) neutral PHMB, a neutral pH protonated PHMB obtained from Lonza.(3) TPU A, Tecothane™ TT1095A, and aromatic polyether TPU of 93 Shore Ahardness commercially available from Lubrizol.(4) TPU B, Tecoflex™ EG93A-B30, an aliphatic polyether TPU of 90 Shore Ahardness commercially available from Lubrizol, modified with aradiopacifier.

Preparation of antimicrobial polymeric compositions: For each example anantimicrobial additive PHMB and a TPU is fed with gravimetric feedersinto a 26 mm twin screw extruder with co-rotating, self-wiping screwswith both conveying and mixing elements and a L/D ratio of 39:1. Thestrands are extruded into a chilled water bath and cut into pellets.Pellets are later compression molded into films or extruded into tubingfor additional testing. Additive loading level was confirmed by NMR andin all cases was essentially equal to the ratio of additives fed intothe extruder. Formulations and performance results are summarized inTable 1.

The Examples shown below are tested for antimicrobial efficacy by thestandard test method JIS Z2801. Results of antimicrobial efficacytesting on various compositions are indicated in Table 1.

The example shown below are also evaluated for their antimicrobial andnon-leaching properties.

The JIS Z 2801 test method is designed to quantitatively test theability of hard surfaces to inhibit the growth of microorganisms or killthem, over a 24 hour period of contact. In the JIS Z 2801 Test: (i) thetest microorganism is prepared, (ii) the suspension of testmicroorganism is standardized by dilution in a nutritive broth, (iii)control and test surfaces are inoculated with microorganisms and themicrobial inoculum is covered with a thin, sterile film, (iv) microbialconcentrations are determined at “time zero” by elution followed bydilution and plating, (v) a control is run with the samples, (vi)samples are incubated undisturbed in a humid environment for 24 hours,(vii) after incubation, microbial concentrations are determined. Thereduction of microorganisms relative to initial concentrations and thecontrol surface is calculated, thus higher results indicate betterantimicrobial performance. The examples were also analyzed by GPC forweight average molecular weight (MW) and poly dispersity index (PDI).The molecular weight was measured using a Waters Model 515 pump GPC witha Waters Model 717 Auto-sampler, a Waters Model 2414 Refractive Index @40° C. using a PLgel Guard+2×Mixed D (5u), 300×7.5 mm column set with aTHF, stabilized with 250 ppm BHT, 1.0 ml/min, @ 40° C. mobile phase andan injection volume of 50 μl (i.e. a concentration ˜0.12%). Themolecular weight calibration curve was established with EasiCalpolystyrene standards from Polymer Laboratories.

TABLE 1 JIS Z2801 JIS Z2801 S. aureus E. coli Formulation (log. Red.)(log. Red.) ZOI MW PDI Example 1 n/a n/a positive 180 k  2.1 TPU AExample 2 >4.8  2.3 negative 92 k 2.5 1% Matrix PHMB in TPU A Example 3n/a n/a positive 73 k 1.9 TPU B Example 4 >5.20 >5.05 negative 81 k 2.14% Lonza PHMB in TPU B

The results show that when free base PHMB (i.e. deprotonated PHMB) isused, antimicrobial performance is significantly improved compared tothe TPU itself. Further the results show that 1% of PHMB in a TPU givecomparable antimicrobial performance to a TPU treated with 4% of aprotonated PHMB.

Table 2 shows additional examples which may be tested for theirantimicrobial performance, where different forms and amounts of PHMB areused:

TABLE 2 % Matrix % Lonza Example TPU PHMB PHMB 2-1 TPU A   0%   0% 2-2TPU A 0.5%   0% 2-3 TPU A   1%   0% 2-4 TPU A   2%   0% 2-5 TPU A   5%  0% 2-6 TPU A   0% 0.5% 2-7 TPU A   0%   1% 2-8 TPU A   0%   2% 2-9 TPUA   0%   5% 2-10 TPU A   1%   1% 2-11 TPU B   0%   0% 2-12 TPU B 0.5%  0% 2-13 TPU B   1%   0% 2-14 TPU B   2%   0% 2-15 TPU B   5%   0% 2-16TPU B   0% 0.5% 2-17 TPU B   0%   1% 2-18 TPU B   0%   2% 2-19 TPU B  0%   5% 2-20 TPU B   1%   1%

Table 3 shows additional examples which may be tested for theirantimicrobial performance, where different processing is used. Anexample marked “hot” means the mixing of the composition is carried outabove 225 degrees Celsius. An example marked “cold” means the mixing ofthe composition is carried out below 170 degrees Celsius.

TABLE 3 % Matrix % Lonza Example TPU PHMB PHMB 3-1 hot TPU A   0%   0%3-2 hot TPU A 0.5%   0% 3-3 hot TPU A   1%   0% 3-4 hot TPU A   2%   0%3-5 hot TPU A   5%   0% 3-6 hot TPU A   0% 0.5% 3-7 hot TPU A   0%   1%3-8 hot TPU A   0%   2% 3-9 hot TPU A   0%   5% 3-10 hot TPU A   1%   1%3-11 cold TPU A   0%   0% 3-12 cold TPU A 0.5%   0% 3-13 cold TPU A   1%  0% 3-14 cold TPU A   2%   0% 3-15 cold TPU A   5%   0% 3-16 cold TPU A  0% 0.5% 3-17 cold TPU A   0%   1% 3-18 cold TPU A   0%   2% 3-19 coldTPU A   0%   5% 3-20 cold TPU A   1%   1%

Each of the documents referred to above is incorporated herein byreference, including any prior applications, whether or not specificallylisted above, from which priority is claimed. The mention of anydocument is not an admission that such document qualifies as prior artor constitutes the general knowledge of the skilled person in anyjurisdiction. Except in the Examples, or where otherwise explicitlyindicated, all numerical quantities in this description specifyingamounts of materials, reaction conditions, molecular weights, number ofcarbon atoms, and the like, are to be understood as modified by the word“about.” It is to be understood that the upper and lower amount, range,and ratio limits set forth herein may be independently combined.Similarly, the ranges and amounts for each element of the technologydescribed herein can be used together with ranges or amounts for any ofthe other elements.

As described hereinafter the molecular weight of the materials describedabove have been determined using known methods, such as GPC analysisusing polystyrene standards. Methods for determining molecular weightsof polymers are well known. The methods are described for instance: (i)P. J. Flory, “Principles of star polymer Chemistry”, Cornell UniversityPress 91953), Chapter VII, pp 266-315; or (ii) “Macromolecules, anIntroduction to star polymer Science”, F. A. Bovey and F. H. Winslow,Editors, Academic Press (1979), pp 296-312. As used herein the weightaverage and number weight average molecular weights of the materialsdescribed are obtained by integrating the area under the peakcorresponding to the material of interest, excluding peaks associatedwith diluents, impurities, uncoupled star polymer chains and otheradditives.

As used herein, the transitional term “comprising,” which is synonymouswith “including,” “containing,” or “characterized by,” is inclusive oropen-ended and does not exclude additional, un-recited elements ormethod steps. However, in each recitation of “comprising” herein, it isintended that the term also encompass, as alternative embodiments, thephrases “consisting essentially of” and “consisting of,” where“consisting of” excludes any element or step not specified and“consisting essentially of” permits the inclusion of additionalun-recited elements or steps that do not materially affect the basic andnovel characteristics of the composition or method under consideration.That is “consisting essentially of” permits the inclusion of substancesthat do not materially affect the basic and novel characteristics of thecomposition under consideration.

While certain representative embodiments and details have been shown forthe purpose of illustrating the subject technology described herein, itwill be apparent to those skilled in this art that various changes andmodifications can be made therein without departing from the scope ofthe subject invention. In this regard, the scope of the technologydescribed herein is to be limited only by the following claims.

What is claimed is:
 1. A process of making an antimicrobial polymercomposition, said process comprising the steps of: a) mixing anantimicrobial additive into a polymeric material, wherein saidantimicrobial additive comprises a deprotonated guanidine compound, adeprotonated biguanidine compound, or a mixture thereof; wherein saidpolymeric material comprises a polymeric backbone made up of urethanelinkages derived from a polyisocyanate and a polyol; and wherein saidmixing occurs under conditions that result in the breaking of a minorityof said urethane bonds resulting in reactive isocyanate groups; andwherein two or more of said reactive isocyanate groups react with saidantimicrobial additive to covalently bond said antimicrobial additiveinto the polymeric backbone of said polymeric material; resulting in anantimicrobial polymer composition.
 2. (canceled)
 3. The process of claim1 wherein said antimicrobial additive comprises deprotonatedpolyhexamethylene biguanide.
 4. The process of claim 1 wherein saidpolymeric material comprises a thermoplastic polyurethane derived from(a) a polyisocyanate component, (b) a polyol component, and (c) anoptional chain extender component.
 5. (canceled)
 6. The process of claim1 wherein said mixing occurs at a temperature between 180 and 225degrees Celsius.
 7. The process of claim 1 wherein said mixing occurs inan extruder where the antimicrobial additive is added to the polymericmaterial and wherein said mixing occurs at a temperature between 180 and225 degrees Celsius, where the extruder comprises a twin screw extruderwith co-rotating, self-wiping screws, with a mixture of conveying andmixing elements, and a length to diameter ratio of 30:1 to 50:1.
 8. Theprocess of claim 1 wherein said antimicrobial additive comprises adeprotonated guanidine compound, a deprotonated biguanidine compound, ora mixture thereof; wherein said reactive isocyanate groups reacts withsaid antimicrobial additive and said polymeric material to covalentlybond said antimicrobial additive to the polymeric backbone of saidpolymeric material; and wherein said mixing occurs at a temperaturebetween 180 and 225 degrees Celsius.
 9. The process of claim 1 whereinsaid antimicrobial additive comprises polyhexamethylene biguanide,deprotonated polyhexamethylene biguanide, or a combination thereof;wherein said polymeric material comprises a thermoplastic polyurethanederived from (a) a diisocyanate, (b) an aromatic polyether polyol, and(c) a butane diol component. wherein said mixing occurs in an extruderwhere the antimicrobial additive is added to the polymeric material andwherein said mixing occurs at a temperature between 180 and 225 degreesCelsius, where the extruder comprises a twin screw extruder withco-rotating, self-wiping screws, with a mixture of conveying and mixingelements, and a length to diameter ratio of 30:1 to 50:1.
 10. Theprocess of claim 1 wherein the resulting antimicrobial polymercomposition is non-leaching as determined by the AATCC 147 Assessment ofAntimicrobial Finishes on Textile Materials: Parallel Streak Method. 11.An antimicrobial polymer composition comprising a polymeric material andan antimicrobial additive selected from the group consisting of guanideand biguanide, wherein said polymeric material comprises a polymericbackbone comprising urethane linkages derived from a polyisocyanate anda polyol; and wherein said antimicrobial additive is covalently bondedinto said polymeric backbone of the polymeric material by two or morelinkages between the nitrogen atoms of the guanide or biguanide and theisocyanate.
 12. The antimicrobial polymer composition of claim 11wherein said antimicrobial additive comprises a deprotonated guanidinecompound, a deprotonated biguanidine compound, or a mixture thereof;wherein said polymeric material comprises a thermoplastic polyurethanederived from (a) a diisocyanate, (b) a polyether polyol, and (c) abutane diol component.
 13. An article comprising an antimicrobialpolymer composition, wherein said antimicrobial polymer compositioncomprises a polymeric material and an antimicrobial additive selectedfrom the group consisting of guanide and biguanide, wherein saidpolymeric material comprises a polymeric backbone comprising urethanelinkages derived from a polyisocyanate and a polyol; and wherein saidantimicrobial additive is covalently bonded into said polymeric backboneof the polymeric material by two or more isocyanate linkages.
 14. Thearticle of claim 13 wherein said antimicrobial additive comprises adeprotonated guanidine compound, a deprotonated biguanidine compound, ora mixture thereof; wherein said polymeric material comprises athermoplastic polyurethane derived from (a) a diisocyanate, (b) apolyether polyol, and (c) butane diol component.
 15. The article ofclaim 13, wherein the antimicrobial polymer composition is coated onto amaterial forming the article.